1998 年度実績報告書

C型肝炎ウイルスに遺伝子導入による心筋症モデルの作製

研究課題

研究課題/領域番号	10470164
研究機関	京都大学
研究代表者	松森昭京都大学, 医学研究科, 助教授 (70135573)
キーワード	C型肝炎ウイルス / 心筋症 / 拡張型心筋症 / 肥大型心筋症 / 心筋炎 / PCR法 / 肝炎 / ウイルス
研究概要	【目的】近年、われわれの研究により、心筋症の病因としてC型肝炎ウイルス(HCV)感染の重要性が明らかになった。拡張型心筋症53例中8例(15.1%)、肥大型心筋症66例中11例(16.7%)において血清HCV抗体が陽性であった。これは虚血性心疾患40例中1例(2.5%)に比し有意に高頻度であった(p<0.05)。SSCP(single strand conformation polymorphism)法による心筋症患者でのゲノム解析では、超可変領域(HVR)め塩基多様度が高度で、多数のクローンが同一症例にみられることがあり、これらの変異により心筋に親和性の高いウイルスゲノムが出現する可能性が考えられた。また、多施設の共同研究としてわが国における心筋症におけるHCV感染およびHCV抗体陽性者の臨床像に関するアンケート調査を行った結果、拡張型心筋症619例中37例(6.0%)、肥大型心筋症585例中61例(10.4%)において血清HCV抗体が陽性であった。一方、HCV抗体陽性者は11,210例中604例(5.4%)に見られた。このHCV抗体陽性例の臨床診断名は不整脈、高血圧症をはじめとして多くの疾患でみられ、HCV感染は心筋症以外の心疾患にも関与している可能性が示唆された。研究代表者はホルマリン固定パラフィン切片がらのHCVゲノム検出法を確定し、剖検心を用いた検討が可能となった。剖検心では心筋炎4/12(33.3%)、拡張型心筋症3/26(11.5%)、肥大型心筋症6/23(26.0%)と高頻度にHCVゲノムに検出した。WHO/世界心臓連盟の心筋症科学委員会による心筋症のウイルス病因に関する国際共同研究において、研究代表者はHCV解析を担当したが、拡張型心筋症および心筋炎の生検標本22例中6例(27.3%)からHCVゲノムを検出し、検討したウイルス中で最も高頻度であった。

研究成果
(18件)

すべてその他

すべて文献書誌 (18件)

[文献書誌] Wang W-Z, et al.: "Protective effects of Mu-Fang-Ji-Tang against myocardial injury in a murine model of congestive heart failure induced by viral myocarditis." Life Sci. 62. 1139-1147 (1998)
[文献書誌] Okada M, et al.: "Cyclical stretch upregulates the prodection of interleukin-8 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in human endothelial cells." Arterioscler Thromb Vasc Biol. 18. 894-901 (1998)
[文献書誌] Ono K, et al.: "Cytokine gene expression after myocardial infarction in rat hearts. Possible implication in left ventricular remodeling." Circulation. 98. 149-156 (1998)
[文献書誌] Matsumori A.: "Calcium channel blocker-induced protection against cardiovascular damage." Int.J.Cardiol.suppl.62. S39-S46 (1998)
[文献書誌] Matsumori A.: "The use of cytokine inhibitors A new therapeutic insight into heart failure." Int.J.Cardiol.suppl.62. S3-S12 (1998)
[文献書誌] Matsumori A, et al.: "Circulating hepatocyte growth factor as an early marker of arterial thrombus formation." Jpn Circ J. 62. 311-313 (1998)
[文献書誌] Matsumori A, et al.: "Hepatitis C virus infection and heart diseases. A multicenter study in Japan." Jpn Circ J. 62. 389-391 (1998)
[文献書誌] Sato Y, et al.: "Serum concentration of cardiac troponin T in patients with cardiomyopathy-A possible mechanism of acute heart failure-" HEART. 80. 209-210 (1998)
[文献書誌] Yamada T, et al.: "Myosin light chain I trade:A simple marker for the severity and prognosis of patients with acute myocardial infarction." Am Heart J. 135. 329-334 (1998)
[文献書誌] Nishio R, et al.: "Denopamine, a β1-adrenergic agonist, prolongs survival in a murine model of congestive heart failure induced by viral myocarditis. Suppression of tumor necrosis factor-a production in the heart." J Am Coll Cardiol. 32. 808-815 (1998)
[文献書誌] Matsumori A, et al.: "Immediate increase in circulating hepatocyte growth factor/scatter factor by heparin." J Mol Cell Cardiol. 30. 2145-2149 (1998)
[文献書誌] Matsumori A, et al.: "Hepatitis C virus infection and hypertrophic cardiomyopathy." Ann Int Med. 129. 749-750 (1998)
[文献書誌] Furukawa Y, et al.: "Anti-monocyte chemoattractant protein-1/monocyte chemotactic and activating factor antibody inhibits neointimal hyperplasia in injured rat carotid arteries." Circ Res. 84. 306-314 (1999)
[文献書誌] Ono K, et al.: "Prevention of myocardial reperfusion injury in rats by an antibody against monocyte chemotactic and activating factor/monocyte chemoattractant protein-1." Lab Invest. 79. 195-203 (1999)
[文献書誌] Okada M, et al.: "Hepatocyte growth factor is a major mediator in heparin-induced angiogenesis." Biochem Biophys Res Commun. 225. 80-87 (1999)
[文献書誌] Iwasaki A, et al.: "Pimobendan inhibits the production of proinflammatory cytokines and gene expression of inducible nitric oxide synthase in a murine model of viral myocarditis." J Am Coll Cardiol. (in press).
[文献書誌] Matsumori A, et al.: "Apical hypertrophic cardiomyopathy and hepatitis C virus infection." Jpn Circ J. (in press).
[文献書誌] Matsumori A,et al.: "Coronary reperfusion and cytokines." Edited by Abiko Y, Karmazyn M Springer-Verlag, Tokyo, 157-177(20) (1998)

1998 年度 実績報告書

C型肝炎ウイルスに遺伝子導入による心筋症モデルの作製

研究代表者

松森 昭 京都大学, 医学研究科, 助教授 (70135573)

研究成果

[文献書誌] Wang W-Z, et al.: "Protective effects of Mu-Fang-Ji-Tang against myocardial injury in a murine model of congestive heart failure induced by viral myocarditis." Life Sci. 62. 1139-1147 (1998)

[文献書誌] Okada M, et al.: "Cyclical stretch upregulates the prodection of interleukin-8 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in human endothelial cells." Arterioscler Thromb Vasc Biol. 18. 894-901 (1998)

[文献書誌] Ono K, et al.: "Cytokine gene expression after myocardial infarction in rat hearts. Possible implication in left ventricular remodeling." Circulation. 98. 149-156 (1998)

[文献書誌] Matsumori A.: "Calcium channel blocker-induced protection against cardiovascular damage." Int.J.Cardiol.suppl.62. S39-S46 (1998)

[文献書誌] Matsumori A.: "The use of cytokine inhibitors A new therapeutic insight into heart failure." Int.J.Cardiol.suppl.62. S3-S12 (1998)

[文献書誌] Matsumori A, et al.: "Circulating hepatocyte growth factor as an early marker of arterial thrombus formation." Jpn Circ J. 62. 311-313 (1998)

[文献書誌] Matsumori A, et al.: "Hepatitis C virus infection and heart diseases. A multicenter study in Japan." Jpn Circ J. 62. 389-391 (1998)

[文献書誌] Sato Y, et al.: "Serum concentration of cardiac troponin T in patients with cardiomyopathy-A possible mechanism of acute heart failure-" HEART. 80. 209-210 (1998)

[文献書誌] Yamada T, et al.: "Myosin light chain I trade:A simple marker for the severity and prognosis of patients with acute myocardial infarction." Am Heart J. 135. 329-334 (1998)

[文献書誌] Nishio R, et al.: "Denopamine, a β1-adrenergic agonist, prolongs survival in a murine model of congestive heart failure induced by viral myocarditis. Suppression of tumor necrosis factor-a production in the heart." J Am Coll Cardiol. 32. 808-815 (1998)

[文献書誌] Matsumori A, et al.: "Immediate increase in circulating hepatocyte growth factor/scatter factor by heparin." J Mol Cell Cardiol. 30. 2145-2149 (1998)

[文献書誌] Matsumori A, et al.: "Hepatitis C virus infection and hypertrophic cardiomyopathy." Ann Int Med. 129. 749-750 (1998)

[文献書誌] Furukawa Y, et al.: "Anti-monocyte chemoattractant protein-1/monocyte chemotactic and activating factor antibody inhibits neointimal hyperplasia in injured rat carotid arteries." Circ Res. 84. 306-314 (1999)

[文献書誌] Ono K, et al.: "Prevention of myocardial reperfusion injury in rats by an antibody against monocyte chemotactic and activating factor/monocyte chemoattractant protein-1." Lab Invest. 79. 195-203 (1999)

[文献書誌] Okada M, et al.: "Hepatocyte growth factor is a major mediator in heparin-induced angiogenesis." Biochem Biophys Res Commun. 225. 80-87 (1999)

[文献書誌] Iwasaki A, et al.: "Pimobendan inhibits the production of proinflammatory cytokines and gene expression of inducible nitric oxide synthase in a murine model of viral myocarditis." J Am Coll Cardiol. (in press).

[文献書誌] Matsumori A, et al.: "Apical hypertrophic cardiomyopathy and hepatitis C virus infection." Jpn Circ J. (in press).

[文献書誌] Matsumori A,et al.: "Coronary reperfusion and cytokines." Edited by Abiko Y, Karmazyn M Springer-Verlag, Tokyo, 157-177(20) (1998)

1998 年度実績報告書

松森昭京都大学, 医学研究科, 助教授 (70135573)